Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Abstract

Nanostructures based on DNA self-assembly present an innovative way to address the increasing need for target-specific delivery of therapeutic molecules. Currently, most of the chemotherapeutics being used in clinical practice have undesired and exceedingly high off-target toxicity. This is a challenge in particular for small molecules, and hence, developing robust and effective methods to lower these side effects and enhance the antitumor activity is of paramount importance. Prospectively, these issues could be tackled with the help of DNA nanotechnology, which provides a route for the fabrication of custom, biocompatible, and multimodal structures, which can, to some extent, resist nuclease degradation and survive in the cellular environment. Similar to widely employed liposomal products, the DNA nanostructures (DNs) are loaded with selected drugs, and then by employing a specific stimulus, the payload can be released at its target region. This review explores several strategies and triggers to achieve targeted delivery of DNs. Notably, different modalities are explained through which DNs can interact with their respective targets as well as how structural changes triggered by external stimuli can be used to achieve the display or release of the cargo. Furthermore, the prospects and challenges of this technology are highlighted.

Tumor microbiome metabolism: A game changer in cancer development and therapy

“…For example, the utilization of biomaterials, such as nanoparticles ( 194 , 195 ) and hydrogels ( 174 ), to modulate and deliver microbial communities to specific sites of the TME opens a new door for future cancer therapies ( Figure 4 ). These novel materials can be designed to be stimuli responsive ( 196 ) and utilized for the controlled and targeted release of toxic chemotherapy drugs ( 197 ), therapeutic antibodies ( 198 , 199 ), CAR-T cells ( 200 , 201 ), or live microbes to reshape the TME ( 202 – 204 ). These applications of new biomaterials will offer a promising platform for basic and translational research and will accelerate clinical outcomes of drugs that may have poor solubility and high toxicity.…”

DNA Nanostructures in Pharmaceutical Applications

“…ImmunostimulatoryCpG ODNs are a special class of therapeutic drugs [24] . These CpG are found on bacterial and viral DNA, when they are exposed during infection, they trigger the Toll‐like receptor(TLR), which triggers a powerful immune response [6] . CpG ODN is delivered using a variety of DNA nanostructures, including DNA tetrahedrons, DNA origami, and so on.…”

Optically Responsive Protein Coating of DNA Origami for Triggered Antigen Targeting

“…20,21 For biomedical applications, several DNA nanostructures have been further functionalized with antibodies, affibodies, and aptamers for targeting purposes. 22 These targeting agents can be site-specifically attached, ensuring an optimal interaction with their receptor which was found to be dependent on the origami shape and orientation. 23 Antibody− antigen interactions can be furthermore studied by immobilization of small-molecule antigens onto the DNA origami surface 24 and can be applied for triggering a conformation change of the origami which is exploited for cargo display, such as drug molecules.…”